title: AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3β (GSK-3β) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane.
abstract: Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3β inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3β inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3β inhibition. Phosphorylation studies demonstrate that afadin is a substrate for AMPK. These data demonstrate that two kinases involved in regulating cell growth and metabolism act through distinct pathways to influence the deposition of the components of epithelial tight junctions.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Francois
authors.initials: F
authors.lastname: Jouret
authors.forename: Jesse
authors.initials: J
authors.lastname: Rinehart
authors.forename: Jeff
authors.initials: J
authors.lastname: Sfakianos
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D008856:Microscopy, Fluorescence / Q000379:methods; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; D002118:Calcium